CN102574810A - Process for the preparation of 4-sulfinyl-pyrazole derivatives - Google Patents
Process for the preparation of 4-sulfinyl-pyrazole derivatives Download PDFInfo
- Publication number
- CN102574810A CN102574810A CN2010800480206A CN201080048020A CN102574810A CN 102574810 A CN102574810 A CN 102574810A CN 2010800480206 A CN2010800480206 A CN 2010800480206A CN 201080048020 A CN201080048020 A CN 201080048020A CN 102574810 A CN102574810 A CN 102574810A
- Authority
- CN
- China
- Prior art keywords
- acid
- compound
- calcium
- barium
- trifluoroacetic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 0 *c(c(*)c1*)c(*)c(*)c1-[n](c(N)c1S*)nc1C#N Chemical compound *c(c(*)c1*)c(*)c(*)c1-[n](c(N)c1S*)nc1C#N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/44—Oxygen and nitrogen or sulfur and nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Epoxy Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The present invention relates to a novel process for the preparation of a compound of formula (I), wherein R1, R2, R3, R4 and R5 are each independently selected from hydrogen, halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, nitro, cyano, and pentafluorothio; R6 is C1-C4-alkyl, or C1-C4-haloalkyl; by oxidation of a compound of formula (II) with an oxidation agent selected from trifluoroperacetic acid and trichloroperacetic acid in the presence of a catalyst selected from hydroxides, oxides, sulfates, acetates or trifluoroacetates of lithium, magnesium, calcium, strontium, barium, titanium (IV), zinc (II) and manganese (II).
Description
The present invention relates to a kind of through in the presence of the catalyzer of the oxyhydroxide, oxide compound, vitriol, acetate or the trifluoroacetate that are selected from lithium, magnesium, calcium, strontium, barium, titanium (IV), zinc (II) and manganese (II) with oxygenant oxidation formula (II) compound and the novel method of preparation formula (I) compound that are selected from trifluoroperacetic acid and trichlorine peroxy acetic acid:
Wherein
R
1, R
2, R
3, R
4And R
5Be selected from hydrogen, halogen, C independently of one another
1-C
4Alkyl, C
1-C
4Haloalkyl, C
1-C
4Alkoxyl group, C
1-C
4Halogenated alkoxy, nitro, cyanic acid and five fluorine sulfenyls; And R
6Be C
1-C
4Alkyl or C
1-C
4Haloalkyl;
R wherein
1, R
2, R
3, R
4, R
5And R
6Such as to formula (I) compound definition.
The 4-sulfinyl pyrazole derivatives of formula (I) is important agricultural chemicals.The 4-sulfinyl pyrazole derivatives that is even more important is special (fipronil) and an ethiprole (ethiprole) of sharp strength.
Preparing some phenyl pyrazoles that has sulfinyl or alkylsulfonyl through the sulfur oxide atom by corresponding alkylthio, alkenyl thio or alkynes sulfur-based compound awards among the EP-A1 295177 usually.As possible oxygenant mention hydrogen peroxide, the trifluoroperacetic acid that forms on the spot by trifluoroacetic anhydride and hydrogen peroxide, trifluoroperacetic acid acid anhydride or the preferred 3-chlorine peroxybenzoic acid in solvent such as methylene dichloride, chloroform, trifluoroacetic acid.Perhaps will provide as oxygenant at potassium hydrogen persulfate in solvent such as methyl alcohol or the water or peroxy-monosulfuric acid sylvite.
Many documents relate to oxidation-type (II) compound with preparation formula (I) compound, and especially sharp strength is special.
In IPCOM000156770D, described in the presence of trifluoroacetic acid with hydrogen peroxide oxidation formula (II) compound as the methylene dichloride of solvent.CN 101250158A mentions in inert solvent (mono chloro benzene, chloroform) with hydrogen peroxide and sulfuric acid catalysis oxidation-type (II) compound, but does not describe the structure of catalyzer.Similarly, in Shanghai Chemical Industry 2007,7 (32), 17, mentioned in methylene dichloride, but do not provided the structural details of catalyzer with catalytic oxidation of hydrogen peroxide formula (II) compound.
CN 101168529A instructed in the solvent mixture of ionic liquid and acetonitrile ruthenium trichloride as in the presence of the catalyzer with trichlorine isocyanic acid oxidation-type (II) compound.Similarly, in Journal of Fluorine Chemistry 2006,127,948, mention in trichlorine isocyanic acid oxidation-type (II) compound as the methylene dichloride of solvent.
WO 2007/122440 has instructed in dichloro acetic acid or methylene dichloride with trichoroacetic acid(TCA)/hydrogen peroxide oxidation formula (II) compound.
WO 2009/077853 has listed many reagent that are used for oxidation-type (II) compound: trifluoroacetic acid and oxone; Trifluoromethanesulfanhydride anhydride in ethanol and hydrogen peroxide; The two hydroperoxide (cyclohexylidenebishydroperoxide) of cyclohexylidene in acetonitrile, Soiodin and hydrogen peroxide; Hexadecyl bromination ammonium (cerammoniumbromide), sodium bromate and silica gel in methylene dichloride; And the hydrogen peroxide in methyl alcohol adds the HAuCl of catalytic amount
4
Oxidation-type (II) compound and the aforesaid method that obtains formula (I) compound are not entirely satisfactory.The standard of suitable extensive method for oxidation is following: the sulfoxide product of (1) high selectivity oxidation accepted way of doing sth (I) (promptly obtains a small amount of sulfone by product, the (=O) R of the S in its Chinese style (I) compound
6-group over oxidation become S (=O)
2R
6-group); (2) formula of high yield (I) compound; (3) owing to forming on the spot, hydrogen fluoride suppresses corrosion in oxidising process; (4) oxidizing reaction rate high (having determined productivity).Up to now, the optimum combination of deal with problems (1), (2) and (3) is discussed by WO01/30760, and it has been described in the presence of corrosion inhibition compound with trifluoroperacetic acid oxidation-type (II) compound.Yet, still can not be high to large-scale industry method desired rate as far as the speed of reaction of this method decision productivity.
Therefore, the purpose of this invention is to provide and a kind of compound (II) is oxidized to the novel of compound (I) and improves one's methods.Particularly, purpose provides and a kind ofly compound (II) is oxidized to the novel of compound (I) and improves one's methods to improve (higher) speed of reaction.In preferred embodiments, purpose provides and a kind of compound (II) Catalytic Oxygen is changed into the novel of compound (I) and improves one's methods, and wherein can catalyzer easily be removed (for example through using water washing) from reaction product.
Therefore, found the defined the inventive method of beginning.Surprising is that the compound that adds the oxyhydroxide, oxide compound, vitriol, acetate or the trifluoroacetate that are selected from lithium, magnesium, calcium, strontium, barium, titanium, zinc and manganese has significantly improved speed of reaction, thereby boosts productivity (product that time per unit is produced).
It is special as the sharp strength of the midbody compound of the sharp strength of preparation butylene special (compound III) that the present invention can be used for preparation.Sharp strength spy of butylene such as CN 3198515 said alkylations through sharp strength spy obtain.
Each substituting group has following meanings:
Term halogen is represented fluorine, bromine, chlorine or iodine in each case, especially fluorine, chlorine or bromine, preferably chlorine or fluorine.
Term " C used herein
1-C
4Alkyl " refer to have the saturated straight chain or the branched hydrocarbyl radical of 1-4 carbon atom, for example methyl, ethyl, propyl group, 1-methylethyl, butyl, 1-methyl-propyl, 2-methyl-propyl and 1,1-dimethyl ethyl.
Term " C used herein
1-C
4Haloalkyl " refer to have the straight chain or the branching saturated alkyl (as stated) of 1-4 carbon atom; and wherein the part or all of Wasserstoffatoms in these groups is replaced by above-mentioned halogen atom, like chloromethyl, brooethyl, dichloromethyl, trichloromethyl, methyl fluoride, difluoromethyl, trifluoromethyl, chlorine methyl fluoride, dichloro one methyl fluoride, a chlorodifluoramethyl-, 1-chloroethyl, 1-bromotrifluoromethane, 1-fluoro ethyl, 2-fluoro ethyl, 2,2-two fluoro ethyls, 2; 2; 2-trifluoroethyl, 2-chloro-2-fluoro ethyl, 2-chloro-2,2-two fluoro ethyls, 2,2-two chloro-2-fluoro ethyls, 2; 2,2-three chloroethyls, pentafluoroethyl group etc.
Term " C used herein
1-C
4Alkoxyl group " refer to the straight chain with 1-4 carbon atom or the branching saturated alkyl (as stated) that connect via Sauerstoffatom.Instance comprises methoxyl group, oxyethyl group, OCH
2-C
2H
5, OCH (CH
3)
2, n-butoxy, OCH (CH
3)-C
2H
5, OCH
2-CH (CH
3)
2And OC (CH
3)
3
Term " C used herein
1-C
4Halogenated alkoxy " refer to above-mentioned C
1-C
4Alkoxyl group, wherein Wasserstoffatoms is partially or completely substituted by fluorine, chlorine, bromine and/or iodine, i.e. for example chlorine methoxyl group, dichloro methoxyl group, trichlorine methoxyl group, fluorine methoxyl group, difluoro-methoxy, trifluoromethoxy, chlorine fluorine methoxyl group, dichloro one fluorine methoxyl group, a chlorine difluoro-methoxy, 2-fluorine oxyethyl group, 2-chloroethoxy, 2-bromine oxethyl, 2-iodine oxyethyl group, 2; 2-difluoroethoxy, 2,2,2-trifluoro ethoxy, 2-chloro-2-fluorine oxyethyl group, 2-chloro-2; 2-difluoroethoxy, 2,2-two chloro-2-fluorine oxyethyl groups, 2,2; 2-three chloroethoxies, five fluorine oxyethyl groups, 2-fluorine propoxy-, 3-fluorine propoxy-, 2,2-difluoro propoxy-, 2,3-difluoro propoxy-, 2-chlorine propoxy-, 3-chlorine propoxy-, 2; 3-dichloro propoxy-, 2-bromine propoxy-, 3-bromine propoxy-, 3,3,3-trifluoro propoxy-, 3; 3,3-trichlorine propoxy-, 2,2; 3; 3,3-five fluorine propoxy-, seven fluorine propoxy-, 1-(methyl fluoride)-2-fluorine oxyethyl group, 1-(chloromethyl)-2-chloroethoxy, 1-(brooethyl)-2-bromine oxethyl, 4-fluorine butoxy, 4-chlorine butoxy, 4-bromine butoxy, nine fluorine butoxy, especially chlorine methoxyl group, fluorine methoxyl group, difluoro-methoxy, trifluoromethoxy, 2-fluorine oxyethyl group, 2-chloroethoxy or 2; 2, the 2-trifluoro ethoxy.
For the inventive method, formula (I) and (II) substituting group of compound preferably have following meanings:
R
1And R
5Be preferably selected from halogen and C
1-C
4Haloalkyl, even more preferably be selected from chlorine, fluorine and trifluoromethyl, most preferably be selected from chlorine.
R
2And R
4Be preferably hydrogen.
R
3Be preferably C
1-C
4Alkyl, C
1-C
4Haloalkyl or five fluorine sulfenyls, even more preferably C
1-C
4Haloalkyl, most preferably trifluoromethyl.
R
6Be preferably ethyl or trifluoromethyl.
R
6Be preferably ethyl.
R
6Most preferably be trifluoromethyl.
Most preferably formula (I) and (II) substituting group of compound have following implication:
R
1And R
5Be chlorine;
R
2And R
4Be hydrogen;
R
3Be trifluoromethyl; With
R
6Be ethyl or trifluoromethyl, preferred trifluoromethyl.
In especially preferred embodiment, the inventive method is used to prepare compound I-1 or the I-2 of scheme I.
Scheme I
Most preferably the inventive method is used to prepare sharp strength spy.
Formula (II) compound can be according to document such as WO 01/30760, and WO 05/44806 obtains with program described in the EP-A1 295117.
Suitable oxygenant is trifluoroperacetic acid (for example being formed on the spot by trifluoroacetic acid and hydrogen peroxide) or trichlorine peroxy acetic acid (for example being formed on the spot by trichoroacetic acid(TCA) and hydrogen peroxide).Preferred trifluoroperacetic acid.Most preferably use the trifluoroperacetic acid that forms on the spot by trifluoroacetic acid and hydrogen peroxide.Hydrogen peroxide uses as the 50 weight % aqueous solution usually and is generally about 1.0-2.0 equivalent with respect to formula (II) compound, preferably about 1.2-1.6 equivalent, 1.30-1.45 equivalent more preferably from about, even 1.35-1.40 equivalent more preferably from about.
The inventive method preferably is being selected from trifluoroacetic acid, carries out in the solvent of the mixture of the mixture of trifluoroacetic acid and mono chloro benzene or trifluoroacetic acid and methylene dichloride and trichoroacetic acid(TCA) and fusing point depressant such as mono chloro benzene, Monochloro Acetic Acid, dichloro acetic acid, ethylene dichloride and methylene dichloride.
If use the mixture of trichoroacetic acid(TCA) and fusing point depressant, then this fusing point depressant uses with the 20-30 weight % of trichoroacetic acid(TCA) usually.Preferred every mole of formula (II) compound uses 1.0-2.0 to rise trichoroacetic acid(TCA).
Preferred solvent is a trifluoroacetic acid.Preferably use about 10-20mol trifluoroacetic acid, more preferably from about 14-16 molar equivalent, most preferably from about 15.2-15.8 molar equivalent with respect to the used molar weight of compound (II).
Of the present invention preferred aspect, trifluoroacetic acid is added mono chloro benzene in the reaction mixture as solvent and when reaction is accomplished, remove trifluoroacetic acid through component distillation then.
This catalyzer is selected from oxyhydroxide, oxide compound, vitriol, acetate or the trifluoroacetate of lithium, magnesium, calcium, strontium, barium, titanium (IV), zinc (II) and manganese (II).
Instance is LiOH (Lithium Hydroxide MonoHydrate), Mg (OH)
2(Marinco H), Ca (OH)
2(calcium hydroxide), Sr (OH)
2(strontium hydroxide), Ba (OH)
2(hydrated barta), Mn (OH)
2(manganous hydroxide (II)), MgOH (Natural manganese dioxide), CaO (quicklime), BaO (barium oxide), TiO
2(titanium oxide), ZnO (zinc oxide (II)), MnO (manganese oxide (II)), trifluoroacetic acid magnesium, calcium trifluoroacetate, trifluoroacetic acid barium; The trifluoroacetic acid strontium, trifluoroacetic acid zinc, trifluoroacetic acid manganese, magnesium acetate, lime acetate; NSC 75794, strontium acetate, zinc acetate, manganous acetate, sal epsom; Calcium sulfate, permanent white, Strontium Sulphate, zinc sulfate, manganous sulfate.
Top listed catalyst that preferably can be commercial.
Metallic cation is preferably selected from the positively charged ion of lithium, magnesium, calcium, strontium, barium, titanium (IV), zinc (II) and manganese (II), most preferably is selected from the positively charged ion of calcium, barium, strontium and zinc (II).Especially preferred positively charged ion is zinc (II).
Preferred catalyzer is selected from the oxyhydroxide of lithium, magnesium, calcium, strontium and barium and the oxide compound of calcium, barium, titanium (IV), zinc (II) and manganese (II).
The oxyhydroxide of preferred, lithium, magnesium, calcium, strontium and barium, especially calcium, strontium and barium.
The oxide compound of preferred calcium, barium, titanium (IV), zinc (II) and manganese (II).Most preferred catalyzer is ZnO and CaO.Especially preferred ZnO.Also especially preferred CaO.
The trifluoroacetate of preferred calcium and zinc (II), especially calcium.
The acetate of also preferred calcium and zinc (II), especially calcium.
The vitriol of preferably magnesium, calcium, strontium, barium and zinc (II), especially calcium, strontium and barium.
The inventive method can be selected from boric acid, alkali metal borate and silicon-dioxide, and the fluoride corrosion suppressor factor of preferred boric acid carries out under existing.In that trifluoroacetic acid is used as under the situation of solvent, advantageously in the presence of the fluoride corrosion suppressor factor, carry out this method.The consumption of corrosion inhibition compound is generally about 0.01-0.99 molar equivalent with respect to formula (II) compound, preferably about 0.01-0.2 molar equivalent, more preferably from about 0.03-0.15 molar equivalent, most preferably from about 0.06-0.1 molar equivalent.
The inventive method is preferably at-40 ℃ to 80 ℃, and more preferably 0-60 ℃, even more preferably 10-30 ℃, even more preferably carry out under 10-20 ℃ the temperature.The inventive method is advantageously carried out under 12 ℃ most preferably at 10-15 ℃.
The advantageous effects that speed of reaction depends on temperature and improves speed of reaction can be observed in whole TR.When according to the inventive method, when promptly in the presence of catalyzer, carrying out, speed of reaction is higher than under uniform temp but does not add the speed of the reaction of carrying out under the catalyzer.
If judge that oxidizing reaction is complete, then preferably stopping with sulfurous gas, S-WAT or reagent of equal value should reaction.With trifluoroacetic acid as under the situation of solvent, preferably through add mono chloro benzene and subsequently under reduced pressure component distillation be removed.In preferred embodiments, alcohol such as ethanol, methyl alcohol or Virahol are added in the resistates and be warmed to about 80 ℃,, be cooled to about 40 ℃ then, this up-to-date style (I) compound crystal up to forming solution.
Necessary, isolating formula (I) compound can be purified through the technology such as chromatography, recrystallize etc.The purification of crude product can also be via on charcoal or silicon-dioxide, filtering or realizing with water washing.
Formula (I) compound such as ethiprole or sharp strength are special, and preferred sharp strength spy's crystallization is usually by having non-reacted substituting group such as chlorine, fluorine, cyanic acid, nitro, C
1-C
8Alkyl or C
1-C
8Solution in nonpolar, the inertia of haloalkyl, the preferred aromatic solvent carries out; Especially preferably undertaken: benzene, ethylbenzene, mono chloro benzene, MONO FLUORO BENZENE, 1 by the solution in following solvent; 2-dichlorobenzene, 1; 3-dichlorobenzene, 1; 4-dichlorobenzene, toluene, o-Xylol, m-xylene, p-Xylol, vinylbenzene, isopropyl benzene, n-propylbenzene, 2-toluene(mono)chloride, 3-toluene(mono)chloride, 4-toluene(mono)chloride, tert.-butylbenzene, sec.-butylbenzene, isobutyl-benzene, n-butylbenzene, 1,3-diisopropyl benzene, 1,4-diisopropyl benzene, 2-nitrotoluene, 3-nitrotoluene, 4-nitrotoluene, oil of mirbane, benzonitrile,
Trifluoromethylbenzene, 1; 2-ethylene dichloride, acetonitrile, methyl-sulphoxide, THF, acetone; Alcohol is like methyl alcohol, ethanol, n-propyl alcohol, Virahol, propyl carbinol, isopropylcarbinol, 2-butanols or the trimethyl carbinol, or its mixture, is preferably undertaken by the solution in mono chloro benzene, dichlorobenzene, ethylbenzene or toluene.
Preferably carry out crystallization by mono chloro benzene.
Preferably carry out crystallization by dichlorobenzene.
Preferably carry out crystallization by ethylbenzene.
Preferably carry out crystallization by toluene.
Possibly advantageously add about 1-30% polar solvent such as ketone, acid amides, alcohols, ester class or ethers; Preferred ester class, ketone or ethers; Like acetone, methyl ethyl ketone, penta-2-ketone, metacetone, 4-methyl-2 pentanone, 3-methyl-2-butanone, tertiary butyl MIBK, pimelinketone, methyl acetate, ETHYLE ACETATE, isopropyl acetate, n-butyl acetate, isobutyl acetate, diethyl carbonate, acetate 2-butoxy ethyl ester, N, N,N-DIMETHYLACETAMIDE, methyl-sulphoxide, Nitromethane 99Min., nitroethane, water, ethanol, methyl alcohol, 1-propyl alcohol, 2-propyl alcohol, 1-butanols, 2-butanols, the trimethyl carbinol, 2-methyl isophthalic acid-propyl alcohol, 2-methyl-2-propyl alcohol, 3-amylalcohol, 2-methyl-1-butene alcohol, 3-methyl isophthalic acid-butanols, 1; 2-terepthaloyl moietie, 1; Ammediol, 1,2-Ucar 35, hexalin, two
alkane, THF, ether, MTBE, 2-methyltetrahydrofuran, acetonitrile, propionitrile or its mixture.
Embodiment
Reaction is carried out to program in embodiment 1,2 and Comparative Examples based on following.Speed of reaction is measured to monitor the former transformation efficiency of expecting required sulfoxide by HPLC in all cases.In case detect sulfide amount＞97% and the just definite reaction end of sulfone amount＞2% by HPLC.
HPLC is being equipped with Chromolith RP18e; The Hewlett Packard HP 1050 of 100 * 3mm post (Merck), Chemstation is last to read eluent: 450mL water+330mL acetonitrile+220mL MeOH+1mL phosphoric acid; Flow velocity: 1.0ml/min detects: 220nm.
Each test is carried out twice.Through corresponding change, use program described in the embodiment 1 and 2 to carry out other preparation tests with different catalysts and/or different catalyst molar equivalent.Test-results is listed in the table below in 1.
Embodiment 1: ZnO as catalyzer in the presence of the sharp strength of preparation special
Sharp strength is special to be passed through with 50 weight % aqueous hydrogen peroxide solution (23.6g; 0.35mol) at trifluoroacetic acid (443.4g; 3.89mol) at ZnO (4.9g; 0.06mol) (105.3g 0.25mol) obtains in 10-12 ℃ of oxidation 5-amino-3-cyanic acid-1-(2,6-dichlor-4-trifluoromethyl phenyl)-4-trifluoromethylthio pyrazoles down in existence.4 hours afterreactions complete (transformation efficiency analyzes＞97% according to HPLC) are used SO then
2Stopping should reaction, adds mono chloro benzene then and removes trifluoroacetic acid through component distillation under reduced pressure.Resistates is by mono chloro benzene/alcohol crystal.Remove ethanol and suspension-s is descended filtration at 10 ℃ through underpressure distillation.With mono chloro benzene, ethanol/water and water washing, vacuum-drying then obtains sharp strength special (96-97g, purity is according to HPLC＞95 weight %) with colorless solid.
Embodiment 2: ZnO as catalyzer in the presence of and adding the corrosion inhibitor sharp strength spy of preparation down
Sharp strength is special to be passed through with 50 weight % aqueous hydrogen peroxide solution (23.6g; 0.35mol) at trifluoroacetic acid (443.4g; 3.89mol) in boric acid (1.3g, 0.02mol) and ZnO (4.9g 0.06mol) exists down in 10-12 ℃ of oxidation 5-amino-3-cyanic acid-1-(2; 6-dichlor-4-trifluoromethyl phenyl)-(105.3g 0.25mol) obtains 4-trifluoromethylthio pyrazoles.4 hours afterreactions complete (transformation efficiency analyzes＞97% according to HPLC) are used SO then
2Stopping should reaction, adds mono chloro benzene then and removes trifluoroacetic acid through component distillation under reduced pressure.Resistates is by mono chloro benzene/alcohol crystal.Remove ethanol and suspension-s is descended filtration at 10 ℃ through underpressure distillation.With mono chloro benzene, ethanol/water and water washing, vacuum-drying then obtains sharp strength special (94-96g, purity is according to HPLC＞95 weight %) with colorless solid.
Comparative Examples: do not adding the sharp strength spy of preparation under the catalyzer
Embodiment 2 said carrying out are as above faced in this reaction, but do not add catalyzer.This was reflected in 6.5 hours accomplishes (transformation efficiency is analyzed greater than 97% according to HPLC).Sharp strength spy obtains (96-97g, purity is according to HPLC＞95 weight %) with colorless solid.
Table 1: it is special to prepare sharp strength
| Embodiment number | Catalyzer | mol | ?B(OH) 3Reinforced [mol] | Temperature [℃] | The reaction deadline [hour] # |
| 1 | ZnO | 0.06 | ?- | 10-12℃ | ?4 |
| 2 | ZnO | 0.06 | ?0.02 | 10-12℃ | ?4 |
| 3 | ZnO | 0.12 | ?- | 10-12℃ | ?3.5 |
| 4 | ZnO | 0.03 | ?- | 10-12℃ | ?4.5 |
| 5 | ZnO | 0.06 | ?- | 5-7℃ | ?6 |
| 6 | ZnO | 0.06 | ?- | 15-17℃ | ?3.5 |
| 7 | CaO | 0.06 | ?- | 10-12℃ | ?3-4 |
| 8 | CaO | 0.06 | ?0.02 | 10-12℃ | ?3-4 |
| 9 | CaO | 0.12 | ?- | 10-12℃ | ?3 |
| 10 | CaO | 0.03 | ?- | 10-12℃ | ?4 |
| 11 | CaO | 0.06 | ?- | 5-7℃ | ?5 |
| 12 | CaO | 0.06 | ?- | 15-17℃ | ?3 |
| 13 | BaO | 0.06 | ?- | 10-12℃ | ?4.5 |
| 14 | MnO | 0.06 | ?- | 10-12℃ | ?6 |
| 15 | TiO 2 | 0.06 | ?- | 10-12℃ | ?6.25 |
| 16 | Ca(OH) 2 | 0.06 | ?- | 10-12℃ | ?4 |
| 17 | Ca(OH) 2 | 0.03 | ?- | 10-12℃ | ?5 |
| 18 | Mg(OH) 2 | 0.06 | ?- | 10-12℃ | ?6 |
| 19 | LiOH | 0.12 | ?- | 10-12℃ | ?6 |
| 20 | Ba(OH) 2 | 0.06 | ?- | 10-12℃ | ?4.5 |
| 21 | Sr(OH) 2 | 0.06 | ?- | 10-12℃ | ?4 |
| 22 | CaSO 4 | 0.06 | ?- | 10-12℃ | ?6 |
| 23 | Lime acetate | 0.06 | ?- | 10-12℃ | ?3.5 |
| Comparative Examples | Do not have | - | ?0.02 | 10-12℃ | ?6.5 |
#Transformation efficiency is analyzed greater than 97% according to HPLC
Claims (10)
1. through in the presence of the catalyzer of the oxyhydroxide, oxide compound, vitriol, acetate or the trifluoroacetate that are selected from lithium, magnesium, calcium, strontium, barium, titanium (IV), zinc (II) and manganese (II), using the method that is selected from oxygenant oxidation formula (II) compound of trifluoroperacetic acid and trichlorine peroxy acetic acid and prepares formula (I) compound:
Wherein
R
1, R
2, R
3, R
4And R
5Be selected from hydrogen, halogen, C independently of one another
1-C
4Alkyl, C
1-C
4Haloalkyl, C
1-C
4Alkoxyl group, C
1-C
4Halogenated alkoxy, nitro, cyanic acid and five fluorine sulfenyls; With
R
6Be C
1-C
4Alkyl or C
1-C
4Haloalkyl;
R wherein
1, R
2, R
3, R
4, R
5And R
6Such as to formula (I) compound definition.
2. according to the process of claim 1 wherein
R
1And R
5Be chlorine;
R
2And R
4Be hydrogen; With
R
3Be trifluoromethyl.
3. according to the method for claim 1 or 2, R wherein
6Be trifluoromethyl or ethyl.
4. according to each method among the claim 1-3; Wherein said method is carried out in being selected from following solvent: trifluoroacetic acid; The mixture of trifluoroacetic acid and mono chloro benzene or trifluoroacetic acid and methylene dichloride, and the mixture of trichoroacetic acid(TCA) and fusing point depressant such as mono chloro benzene, Monochloro Acetic Acid, dichloro acetic acid, ethylene dichloride and methylene dichloride.
5. according to each method among the claim 1-4, wherein said method is carried out in as the trifluoroacetic acid of solvent.
6. according to each method among the claim 1-5, wherein said metallic cation is selected from the positively charged ion of lithium, magnesium, calcium, strontium, barium, titanium (IV), zinc (II) and manganese (II).
7. according to each method among the claim 1-6, wherein said catalyzer is selected from the oxyhydroxide of lithium, magnesium, calcium, strontium and barium and the oxide compound of calcium, barium, titanium (IV), zinc (II) and manganese (II).
8. according to each method among the claim 1-7, wherein said catalyzer is ZnO or CaO.
9. according to each method among the claim 1-8, wherein said method is carried out being selected from the presence of the fluoride corrosion suppressor factor of boric acid, alkali metal borate and silicon-dioxide.
10. according to each method among the claim 1-9, wherein said method is carried out under 0-40 ℃ temperature.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP09174558.8 | 2009-10-30 | ||
| EP09174558 | 2009-10-30 | ||
| PCT/EP2010/066162 WO2011051284A1 (en) | 2009-10-30 | 2010-10-26 | Process for the preparation of 4-sulfinyl-pyrazole derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102574810A true CN102574810A (en) | 2012-07-11 |
| CN102574810B CN102574810B (en) | 2015-01-28 |
Family
ID=43242168
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201080048020.6A Expired - Fee Related CN102574810B (en) | 2009-10-30 | 2010-10-26 | Process for the preparation of 4-sulfinyl-pyrazole derivatives |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US8476459B2 (en) |
| EP (1) | EP2493860B1 (en) |
| JP (1) | JP2013509372A (en) |
| CN (1) | CN102574810B (en) |
| AU (1) | AU2010311536A1 (en) |
| BR (1) | BR112012009611A2 (en) |
| DK (1) | DK2493860T3 (en) |
| IL (1) | IL219138A0 (en) |
| WO (1) | WO2011051284A1 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2011277946B2 (en) * | 2010-07-12 | 2015-06-11 | Adama Makhteshim Ltd. | Fipronil production process |
| BRPI1104747B1 (en) | 2011-09-14 | 2017-11-28 | Rotam Agrochem International Company Limited | PROCESS FOR PREPARATION OF N-SUBSTITUTED PYRAZOLE COMPOUNDS |
| JP5822349B2 (en) * | 2011-12-02 | 2015-11-24 | 公立大学法人首都大学東京 | Oxidation catalyst for organic sulfur compounds |
| CN102633722B (en) * | 2012-03-20 | 2015-05-06 | 金坛市凌云动物保健品有限公司 | Fipronil preparation method |
| JP6086622B2 (en) * | 2015-06-16 | 2017-03-01 | 公立大学法人首都大学東京 | Oxidation catalyst for organic sulfur compound, method for producing oxidation catalyst for organic sulfur compound, method for selectively oxidizing organic sulfur compound |
| CN114573509A (en) * | 2022-03-28 | 2022-06-03 | 江苏托球农化股份有限公司 | Green production process of fipronil |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1332730A (en) * | 1999-10-22 | 2002-01-23 | 阿方蒂农科股份有限公司 | Process for preparing insecticide |
| WO2007122440A1 (en) * | 2006-04-25 | 2007-11-01 | Gharda Chemicals Limited | Process for the preparation of fipronil, an insecticide, and related pyrazoles |
| WO2009077853A1 (en) * | 2007-12-19 | 2009-06-25 | Vétoquinol | Process for the preparation of fipronil and analogues thereof |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8713768D0 (en) | 1987-06-12 | 1987-07-15 | May & Baker Ltd | Compositions of matter |
| FR2616569B1 (en) | 1987-06-12 | 1989-09-08 | Thomson Csf | VISUALIZATION DEVICE WITH MULTIPLE FLAT SCREENS |
| BRPI0416107A (en) | 2003-11-07 | 2007-01-02 | Cheminova As | process of preparation of a trifluoromethyl thioether |
| CN101168529B (en) | 2006-10-24 | 2011-03-23 | 温州大学 | Fipronil, ethiprole and synthesizing method for derivative thereof |
| CN101250158B (en) | 2008-04-02 | 2011-12-07 | 湖南化工研究院 | Preparation method of fipronil |
| EP2443093B8 (en) | 2009-03-16 | 2013-10-09 | Basf Se | Process for the preparation of pyrazole derivatives |
| CN103198515B (en) | 2013-04-18 | 2016-05-25 | 北京尔宜居科技有限责任公司 | In a kind of instant adjusting 3D scene, object light is according to the method for rendering effect |
-
2010
- 2010-10-26 AU AU2010311536A patent/AU2010311536A1/en not_active Abandoned
- 2010-10-26 WO PCT/EP2010/066162 patent/WO2011051284A1/en active Application Filing
- 2010-10-26 BR BR112012009611A patent/BR112012009611A2/en not_active IP Right Cessation
- 2010-10-26 US US13/504,574 patent/US8476459B2/en not_active Expired - Fee Related
- 2010-10-26 EP EP10773615.9A patent/EP2493860B1/en not_active Not-in-force
- 2010-10-26 DK DK10773615.9T patent/DK2493860T3/en active
- 2010-10-26 CN CN201080048020.6A patent/CN102574810B/en not_active Expired - Fee Related
- 2010-10-26 JP JP2012535787A patent/JP2013509372A/en not_active Withdrawn
-
2012
- 2012-04-15 IL IL219138A patent/IL219138A0/en unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1332730A (en) * | 1999-10-22 | 2002-01-23 | 阿方蒂农科股份有限公司 | Process for preparing insecticide |
| WO2007122440A1 (en) * | 2006-04-25 | 2007-11-01 | Gharda Chemicals Limited | Process for the preparation of fipronil, an insecticide, and related pyrazoles |
| WO2009077853A1 (en) * | 2007-12-19 | 2009-06-25 | Vétoquinol | Process for the preparation of fipronil and analogues thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| US8476459B2 (en) | 2013-07-02 |
| EP2493860B1 (en) | 2014-01-15 |
| EP2493860A1 (en) | 2012-09-05 |
| WO2011051284A1 (en) | 2011-05-05 |
| CN102574810B (en) | 2015-01-28 |
| BR112012009611A2 (en) | 2015-09-29 |
| IL219138A0 (en) | 2012-06-28 |
| AU2010311536A1 (en) | 2012-05-31 |
| US20120215008A1 (en) | 2012-08-23 |
| DK2493860T3 (en) | 2014-04-07 |
| JP2013509372A (en) | 2013-03-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102574810A (en) | Process for the preparation of 4-sulfinyl-pyrazole derivatives | |
| EP2542531B1 (en) | Process for synthesis of fipronil | |
| CN101842348B (en) | Process for preparation of trifluoromethanesulfonyl fluoride | |
| CN105967986B (en) | The synthetic method of 3- hydroxy acetophenone | |
| CN103539671A (en) | Method for preparing roflumilast intermediate | |
| EP3976591B1 (en) | Methods for the preparation of 5-bromo-2-(3-chloro-pyridin-2-yl)-2h-pyrazole-3-carboxylic acid | |
| JP2008162902A (en) | Method for producing difluoroacetic acid ester | |
| CN105384668B (en) | The method for being used to prepare ether compound | |
| DK2931703T3 (en) | METHOD FOR PREPARING BIS (3-AMINOPHENYL) -DISULPHIDES AND 3-AMINOTHIOLS | |
| JPWO2018180944A1 (en) | Method for producing halogen-containing pyrazolecarboxylic acid | |
| EA007327B1 (en) | A process for the preparation of modafinil | |
| EP3604282A1 (en) | Method for producing halogen-containing pyrazol carboxylic acid and intermediate thereof | |
| WO2007012183A1 (en) | Process for the production of bicalutamide | |
| KR20200014305A (en) | Process for preparing 3-aryl propion amide compound and 3-aryl propionic acid ester compound | |
| JP5663482B2 (en) | Method for producing pyrimidinylacetonitrile derivative and synthetic intermediate thereof | |
| JP2009155248A (en) | Method for producing acid fluorides | |
| WO2022164988A1 (en) | Method for preparing tert-butyl n-((1r,2s,5s)-2-((2-((5-chloropyridin-2-yl)amino)-2-oxoacetyl)amino)-5-(dimethylcarbamoyl)cyclohexyl)carbamate | |
| US20110218363A1 (en) | Method for producing alkenyl mercaptan | |
| JP2005314356A (en) | Method for production of fluoroalykylfluoroalkane-sulfonate | |
| JP6434261B2 (en) | Iodobenzamide type alcohol oxidation catalyst | |
| JP2022552276A (en) | Method for preparing 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carboxylic acid | |
| CN108947797A (en) | A kind of preparation method of chlorine phenoxy carboxylic acid herbicides | |
| JP3573245B2 (en) | Method for producing 2,4,5-trifluoro-3-trifluoromethylbenzoic acid esters | |
| PT1327623E (en) | Process for the production of dichloro hydroquinone ethers | |
| JP2020037522A (en) | Production method for n,n'-disubstituted biotin compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20150128 Termination date: 20161026 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |